Department of Pediatrics, School of Medicine, University of California Irvine, Hewitt Hall Rm. 2066, Irvine, CA, 92697, USA.
Department of Neurology, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA, 120 Walter P Martin Research Center, Torrance, California, 90502, USA.
Acta Neuropathol Commun. 2024 Aug 7;12(1):126. doi: 10.1186/s40478-024-01840-w.
Traumatic brain injury (TBI) survivors face debilitating long-term psychosocial consequences, including social isolation and depression. TBI modifies neurovascular physiology and behavior but the chronic physiological implications of altered brain perfusion on social interactions are unknown. Adult C57/BL6 male mice received a moderate cortical TBI, and social behaviors were assessed at baseline, 3-, 7-, 14-, 30-, and 60-days post injury (dpi). Magnetic resonance imaging (MRI, 9.4T) using dynamic susceptibility contrast perfusion weighted MRI were acquired. At 60dpi mice underwent histological angioarchitectural mapping. Analysis utilized standardized protocols followed by cross-correlation metrics. Social behavior deficits at 60dpi emerged as reduced interactions with a familiar cage-mate (partner) that mirrored significant reductions in cerebral blood flow (CBF) at 60dpi. CBF perturbations were dynamic temporally and across brain regions including regions known to regulate social behavior such as hippocampus, hypothalamus, and rhinal cortex. Social isolation in TBI-mice emerged with a significant decline in preference to spend time with a cage mate. Cortical vascular density was also reduced corroborating the decline in brain perfusion and social interactions. Thus, the late emergence of social interaction deficits mirrored the reduced vascular density and CBF in regions known to be involved in social behaviors. Vascular morphology and function improved prior to the late decrements in social function and our correlations strongly implicate a linkage between vascular density, cerebral perfusion, and social interactions. Our study provides a clinically relevant timeline of alterations in social deficits alongside functional vascular recovery that can guide future therapeutics.
创伤性脑损伤（TBI）幸存者面临着衰弱的长期心理社会后果，包括社交孤立和抑郁。TBI 改变了神经血管生理学和行为，但改变脑灌注对社交互动的慢性生理影响尚不清楚。成年 C57/BL6 雄性小鼠接受中度皮质 TBI，并在基线、3、7、14、30 和 60 天（dpi）后评估社交行为。使用动态对比增强磁共振灌注加权成像（MRI，9.4T）采集磁共振成像（MRI）。在 60dpi 时，对小鼠进行血管造影结构映射。分析利用标准化协议，然后进行互相关度量。60dpi 时出现的社交行为缺陷表现为与熟悉的笼内伙伴（同伴）的互动减少，这与 60dpi 时大脑血液流量（CBF）的显著减少相吻合。CBF 扰动具有时间上的动态性和跨脑区，包括调节社交行为的已知区域，如海马体、下丘脑和嗅皮层。TBI 小鼠出现社交隔离，与笼内伙伴共度时光的偏好显著下降。皮质血管密度也降低，这与脑灌注和社交互动的下降相吻合。因此，社交互动缺陷的迟发性出现反映了已知参与社交行为的区域的血管密度和 CBF 的降低。血管形态和功能在社交功能的后期下降之前得到改善，我们的相关性强烈表明血管密度、脑灌注和社交互动之间存在联系。我们的研究提供了一个与临床相关的社交缺陷改变的时间线，以及功能血管恢复，这可以为未来的治疗提供指导。
